4- Thursday Pharmacotherapy News – 28th October

1 – Use of Pediatric Injectable Medicines Guidelines and Associated Medication Administration Errors: A Human Reliability Analysis

• In a recent human reliability analysis (HRA) of simulated pediatric resuscitations, ineffective retrieval of preparation and administration instructions from online injectable medicines guidelines was a key factor contributing to medication administration errors (MAEs).
• The aim of the present study was to use a specific HRA to understand where intravenous medicines guidelines are vulnerable to misinterpretation, focusing on deviations from expected practice (discrepancies) that contributed to large-magnitude and/or clinically significant MAEs.
• Discrepancies during the use of an online injectable medicines guideline were often associated with subsequent MAEs, including those with potentially significant consequences.
• This highlights the need to test the usability of guidelines before clinical use.

Source: SAGE Journal

2 – Mechanisms of induction of tumors by cholesterol and potential therapeutic prospects

• Increasing evidence suggested that cholesterol is an important integrant of cell membranes, that plays a key role in tumor progression, immune dysregulation, and pathological changes in epigenetic mechanisms.
• Based on these theories, there is a growing interest on targeting cholesterol in the treatment of cancer.
• Here, they comprehensively reviewed the major function of cholesterol on oncogenicity, the therapeutic targets of cholesterol and its metabolites in cancer, and provide detailed insight into the essential roles of cholesterol in mediating immune and epigenetic mechanisms of the tumor microenvironment.

Source: ScienceDirect

3 – Sterilizing Immunity against COVID-19: Developing Helper T cells I and II activating vaccines is imperative

• Six months after the publication of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) sequence, a record number of vaccine candidates were listed, and quite a number of them have since been approved for emergency use against the novel coronavirus disease 2019 (COVID-19).
• Here, they discuss the immune responses to viral infection with emphasis on COVID-19, and the specific adaptive immune response to SARS-CoV-2 and how it can be harnessed to develop COVID-19 vaccines capable of conferring sterilizing immunity.
• They further propose factors that could be considered in the development of COVID-19 vaccines capable of stimulating sterilizing immunity.
• Also, an old, but effective vaccine development technology that can be applied in the development of COVID-19 vaccines with sterilizing immunity potential is reviewed.

Source: ScienceDirect

4- Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential

• The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science.
• Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection.
• For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to hyperinflammation, and cytokine storm may make these patients susceptible to a more severe course of COVID-19 disease.
• Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK.
• Therefore, activation of AMPK and/or inhibition of the mTOR-mediated signaling pathway may be an important new target for drug therapy in COVID-19 cases mostly by reducing the level of pro-inflammatory signaling and cytokine storm.
• These suggestions have been partially confirmed by several retrospective analyzes of patients with diabetes mellitus hospitalized for severe COVID-19.

Source: ScienceDirect

5 – The role of natural antioxidants in cisplatin-induced hepatotoxicity

• Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses.
• In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver.
• This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.

Source: ScienceDirect

6 – Safety and efficacy of alpha-lipoic acid oral supplementation in the reduction of pain with unknown etiology: A monocentric, randomized, double-blind, placebo-controlled clinical trial

• Extensive evidence suggests that alpha-lipoic acid (ALA) is effective in diabetic neuropathy pain management.
• However, little is known on its safety and efficacy in reducing idiopathic pain in normoglycemic subjects.
• The aim of this study was to evaluate ALA food supplement safety and efficacy in the reduction of different forms of idiopathic pain.
• Since the management of idiopathic pain is challenging for physicians, the use of ALA food supplements could be a feasible option, based on its safety and efficacy compared to commonly-used analgesic drugs.

Source: ScienceDirect

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